吲哒帕胺联合小剂量替米沙坦治疗高血压逆转左心室肥厚的临床观察

目的 探讨吲哒帕胺联合小剂量替米沙坦治疗高血压、逆转左心室肥厚的临床疗效。方法 共入选61例高血压左室肥厚患者，随机分入对照组（吲哒帕胺2．5mg／d，n=21）、治疗组（吲哒帕胺2．5mg／d＋替米沙坦20mg／d，n=30）和吲哒帕胺2．5mg／d＋替米沙坦40mg／d，n=10），疗程均为6个月。观察前后的血压、左心室肥厚的逆转、电解质变化、血脂血糖以及不良反应。结果 ①对照组血压控制达标，有3例在疗程中出现低血钾（占15％），经补充口服10％氯化钾溶液30ml／d完成疗程。而本组左室肥厚逆转情况不理想（P值〉0．05）。②治疗组除10例将替米沙坦剂量增至40mg／d后，所有病例血压均达标。无1例出现电解质的明显异常（无高血钾或低血钾症）。无咳嗽、眩晕出现。左室肥厚逆转明显（P值〈0．05）。结论 在高血压治疗中一天一次联合服用吲哒帕胺加小剂量替米沙坦能够使血压达标，而且可以逆转其左心室肥厚。患者依从性较好。     

硝苯地平及氨氯地平和美托洛尔治疗老年原发性高血压的成本－效果分析

目的分析硝苯地平、苯磺酸氨氯地平和美托洛尔3种不同药物治疗老年原发性高血压的成本一效果。方法将180例老年原发性高血压患者完全随机分为硝苯地平组、苯磺酸氨氯地平组及美托洛尔组，每组60例。硝苯地平组予以硝苯地平治疗，1次／d，30mg／次；苯磺酸氨氯地平组予以氨氯地平治疗，5mg／次，1次／d；美托洛尔组予以美托洛尔治疗，50mg／次，2次／d。治疗8周后，比较3组患者临床疗效，计算成本并进行成本一效果分析。结果苯磺酸氨氯地平组有效率明显高于硝苯地平组、美托洛尔组[95．0％（57／60）比85．0％（51／60）、78．3％（47／60）]，差异有统计意义（P〈0．05）。硝苯地平组、苯磺酸氨氯地平组及美托洛尔组成本一效果比分别为3．57、2．32、1．54，增量成本．效果比硝苯地平组、苯磺酸氨氯地平组分别为18．22、5．94。结论3种药物中，氨氯地平是治疗老年原发性高血压经济有效的最佳选择。     

替米沙坦对高血压病伴代谢综合征的老年患者代谢紊乱的影响

目的探讨替米沙坦对高血压病伴代谢综合征的老年患者代谢紊乱的影响。方法将高血压伴代谢综合征的老年患者完全随机分为替米沙坦组和硝苯地平控释片组。每组20例,分别口服替米沙坦40mg,1次／d,硝苯地平控释片30mg,1次／d,均用药6个月,观察用药前、后空腹血糖,空腹胰岛素,胰岛素抵抗指数,TG,TC,HDL—C,LDL—C等糖、脂代谢指标。结果替米沙坦组用药后血压较用药前明显降低,收缩压平均降低（21．3±12．7）mmHg（P=0．00）,舒张压平均降低（12．8±1．0）mmHg（P=0．00）。硝苯地平控释片组用药后血压较用药前也明显降低,收缩压平均降低（21．5±7．8）mmHg（P=0．00）,舒张压平均降低（9．0±13．1）mmHg（P=0．00）。用药6个月后,2组间比较,血压无统计学差异。替米沙坦组用药6个月后胰岛素抵抗指数较用药前明显降低[（1．83±0．68）vs（2．37±1．10）,P〈0．05],硝苯地平控释片组用药前后无统计学差异。结论替米沙坦可以改善高血压伴代谢综合征的老年患者的胰岛素抵抗。     

替米沙坦致肌痛关节僵硬一例

患者女,50岁,诊断:慢性肾功能衰竭,CKD5期,肾性高血压,维持性血液透析(每周透析2次,每次透析4.5h),患者开始口服硝苯地平缓释片20 mg,每日3次,酒石酸美托洛尔25 mg,每日2次,盐酸特拉唑嗪4 mg,每日1次治疗,血压控制不理想,后在严密监测血钾及规律血液透析情况下,加用替米沙坦40 mg,每日1次,1周后血压逐渐下降至140/90 mm Hg以下,患者无任何不适反应,于用药12周后,出现肌肉疼痛、关节僵硬、流涕等症状,给予查甲状旁腺素,排除甲状旁腺功能亢进引起的肌肉、关节痛,嘱停用替米沙坦,继续规律血液透析治疗,1周后关节疼痛、关节僵硬、流涕等症状消失.     

替米沙坦治疗轻中度原发性高血压疗效和安全性观察

目的观察替米沙坦治疗轻中度原发性高血压病的疗效和安全性。方法采用随机双百平行对照试验的方法将符合条件的轻中度原发性高血压患者66例分为替米沙坦组和培哚普利组各33例，2组分别口服替米沙坦80mg和培哚普利4mg，均1次／d，疗程共8周。结果①治疗8周后，替米沙坦组降压总有效率72．7％，培哚普利组总有效率68．8％，2组差异无统计学意义（P〈0．05）。②治疗前后收缩压、舒张压下降幅度分别为：替米沙坦组11．4％和12．3％，培哚普利组8．9％和11．1％，2组比较无统计学意义（P〉0．05）。③不良反应的发生率，替米沙坦组为3．2％，培哚普利组为15．2％，2组差异有统计学意义（P〈0．05）。结论替米沙坦治疗轻中度原发性高血压安全有效，不良反应发生率低于培哚普利。     

替米沙坦和美托洛尔改善高血压LVH和心功能的疗效观察

目的观察联合应用替米沙坦和美托洛尔对高血压LVH和心功能的影响。方法采用自身对照开放试验方法,102例原发性高血压并左室肥厚、左心室舒张功能不全的患者予口服替米沙坦80mg,1次/d,美托洛尔12.5mg,2次/d连服24周,用超声心动图观察治疗前后左室舒张末内径和左心室舒张功能IVST)、峰值速度A/峰值速度E(A/E)比值均明显下降(P<0.05)。结论联合应用替米沙坦和美托洛尔能有效地控制血压、逆的变化。结果替米沙坦和美托洛尔能有效降低血压,与治疗前相比,患者左室舒张末内径(LVDd)、室间隔舒张末期厚度(转左室肥厚、改善左心室舒张功能。     

ACEI联合CCB降压治疗老年高血压合并糖尿病的临床研究

目的探讨卡托普利与硝苯地平联合治疗老年高血压合并糖尿病的临床疗效及安全性。方法选取2012年4月至2013年6月我院收治的老年高血压合并2型糖尿病患者96例,分为观察组和对照组,各48例,对照组给予单药卡托普利12．5-25mg,3次／d;观察组患者在此基础上再给予硝苯地平控释片30mg,30mg／次,1次／d,10d一疗程,4个疗程后观察,临床疗效、各项指标变化情况及不良反应,分析对比。结果观察组有效率为95．83％,明显高于对照组的有效率85．42％（P〈0．05）;两组患者治疗后血压、肌酐、尿蛋白指标较治疗前均有显著下降,观察组下降幅度明显高于对照组（P〈0．05）。结论联合治疗高血压合并糖尿病安全有效,不良反应少,值得推广使用。     

替米沙坦单用或与雷米普利联用治疗高血压

目的：探讨替米沙坦和雷米普利单用或联合用药治疗原发性轻、中度高血压的疗效和安全性。方法：158例轻、中度原发性高血压患者随机分为替米沙坦80mg·d^-1组、雷米普利5mg·d^-1组和替米沙坦80mg·d^-1＋雷米普利2．5mg·d^-1组,治疗8周后比较三组患者降压的总有效率,观察不良反应。结果：治疗后各组血压明显降低（P〈0．05）,单用组间差异无统计学意义（P〉0．05）,而联合用药组较单独用药组更明显（P〈0．01）。替米沙坦和联合用药组的不良反应少见。结论：替米沙坦和雷米普利联合用药可以有效控制轻、中度原发性高血压,安全性好。     

硝苯地平缓释片联合美托洛尔治疗原发性高血压病的疗效观察

目的探讨在临床上硝苯地平缓释片与美托洛尔联合应用治疗原发性高血压的疗效。方法2010年5月至2012年5月内科门诊及住院部部分原发性高血压病人200例,随机分为治疗组100例,对照组100例,治疗组患者100例给予两药联用,即硝苯地平缓释片20mg,1次／d;美托洛尔25mg,2次／d。而对照组仅给予硝苯地平缓释片单味药物20mg,1次／d,8周后观察两组疗效。结果通过对200例患者服用降压药后的观察,治疗组的心率下降、降压效果以及舒张压（DBP）、收缩压（SBP）的平均下降幅度均优于对照组（P〈0．01）。结论临床上治疗原发性高血压应用硝苯地平缓释片与美托洛尔联合治疗以后降压稳定,效果好,而且能降低心率,不良反应少,值得临床医生对两种药物的联合治疗高血压推广、使用。     

替米沙坦对高血压冠心病患者血浆炎症细胞因子的调节作用

目的探讨替米沙坦对高血压冠心病患者血浆炎症细胞因子的影响。方法将70例原发性高血压1,2级伴稳定型冠心病的患者随机分为治疗组和对照组各35例。两组均予以冠心病常规治疗,治疗组加用替米沙坦,对照组加用硝苯地平缓释片。结果两组均在8周内均实现血压达标．两组血压达标情况无明显差异（P〉0．05）。治疗前,两组hs—CRP、IL-6和TNF-α含量基本一致（P〉0．05）。治疗8周后。两组hs．CRP、IL-6、TNF-α含量均明显下降（均P〈0．05）,但治疗组hs-CRP、IL-6、TNF—α下降程度较对照组更明显（均P〈0．05）。结论替米沙坦降压效果理想,安全可靠,对高血压冠心病患者的血浆hs—CRP、IL-6和TNF-α含量有一定的调节作用,有助于改善此类患者的预后。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Disease control in asthmatic children seen in private practice in Switzerland

ABSTRACT

Background: Asthma is the most common chronic childhood disease in Switzerland with a prevalence of 10%. Asthma has a high economic burden accounting for high medical costs. Assessment of disease control is likely to be of help in the implementation of strategies to improve asthma. Therefore, we aimed to evaluate asthma control and therapy regimens among children in private practice.

Methods: We assessed asthma control as well as therapy regimens in 575 asthmatic children in an experience programme in Switzerland by using an abbreviated questionnaire based on the asthma control questionnaire and the child health questionnaire on Visit 1 and Visit 2.

Results: Good asthma control at Visit 1 was only present in 25.7% of asthmatic children. Occasional asthma symptoms, limitation of physical activity, nocturnal awakening and anxiety of the parent was present in 80.5%, 41.2%, 46.8% and 57% of the children, respectively. After adjustment of therapy regimens at Visit 1, mainly by adding a leukotriene receptor antagonist, asthma control was reported to be much better in 53.4% of the children at Visit 2.

Conclusions: As asthma control is inadequately achieved within a major portion of asthmatic children, it is imperative to find measures to improve asthma control and hence, to reduce the burden of disease.